Haemophilus influenzae
is a Gram-negative, non-motile coccobacillus bacterium
belonging to thePasteurellaceae family of pathogens.
In its encapsulated form, H. influenzae is
relatively small, ranging from 0.2 to 0.8 μm in
size, while the unencapsulated strain exhibits a
longer, more threadlike morphology (Figure 1).
The bacteria is transmitted through close contact with
exposed individuals. Infants and young children
are most at risk. The name Haemophilus
influenzae refers to the bacteria's
requirement of blood factors for growth and to
its association with viral infections such as
influenza.

Figure 1. A
Photomicrograph of Haemophilus influenzae
as seen using a Gram-stain technique.

H. influenzae is
part of the natural flora of the respiratory
tract and most children develop immunity. In
fact, it is present in the nasopharynx of
approximately 75% of healthy children and
adults. It is usually the unencapsulated strain
that is harbored by the natural flora of the
respiratory tract, but a minority of healthy
individuals intermittently harbor H.
influenzae type-B (HiB), the
encapsulated strain, in the upper respiratory
tract. A
large colony of HiB or a concomitant viral infection can trigger the invasive disease.
Diseases from serotype-b H. influenzae
are transmitted via direct contact with
respiratory droplets from a nasopharyngeal
carrier or an infected individual.

H. influenzae has a
polysaccharide outer capsule consisting of
repeating polymers of riboysl and ribitol
phosphate. The presence of this capsular antigen
in body fluids is used to diagnose the disease.

The H. influenzae is
anti-phagocytic. Some strains of H.
influenzae have developed a
plasmid-mediated resistance to many antibiotics,
including ampicillin, the primary therapy for
the infection. The bacilli attach to the
respiratory epithelium lining the alveoli. They
enter the bloodstream by breaking down the tight
junctions between the epithelial cells of the
capillaries. In addition, the bacteria's outer
membrane lipooligosaccharide (LOS) is also
believed to participate in inflammation related
to otitis media (ear infection). All
virulent strains produce neuraminidase and an
IgA (immunoglobulin-A) protease, but the
function of these extracellular enzymes in
invasion is unconfirmed. Fimbriae improve the
adherence of the bacteria to human mucosal cells
in vitro. They are also necessary for
successful colonization of the nasopharynx. The
Anton antigen present in red blood cells appears
to be the receptor.

Metastatic
seeding can lead to bacterial
meningitis,
pneumonia, and neurological disorders. 5% of
invasive infections result in death, while 15%
to 30% cause neurological handicaps. In the
United States, up to 20% of H. influenzae-induced
meningitis-surviving patients have permanent
hearing loss. In addition, in children under the
age of five, H. influenzae may also
cause epiglottis,
osteomyelitis,
joint infections, ear infections, and
sinusitis.
HiB could also cause purulent
pericarditis
and endocarditis.

In order to protect oneself from this pathogen,
a purified surface antigen vaccine is required
for immunization. The H. influenzae
capsular polysacchardise, unique to the type b
strain, gives anti-phagocytic protection to the
pathogen and contributes to the virulence of the
disease.

The polyribosylribitol phosphate (PRP)
polysaccharide vaccine was introduced in 1985.
The polysaccharide alone was poorly immunogenic
in young children and led to the development of
the PRP-protein conjugate vaccines. The
diphtheria toxoid is used as the protein moiety.
Other conjugate preparations are more effective
in infant immunization, such as the
oligosaccharide-diphtheria variant conjugate,
the PRP-Neisseria meningitidis outer membrane
protein conjugate , and the PRP-tetanus toxoid
conjugate. These vaccines are very effective and
have few side effects.